Stereoselective binding of the glucuronide conjugates of carprofen enantiomers to human serum albumin

Biochem Pharmacol. 1990 Mar 1;39(5):949-53. doi: 10.1016/0006-2952(90)90212-4.

Abstract

The stereoselective binding of carprofen enantiomers and carprofen glucuronide diastereomers to human serum albumin (HSA) was studied using an ultrafiltration method. Carprofen glucuronides exhibit a considerable and stereoselective affinity to HSA, although less than that seen for the parent enantiomers. The (S)-glucuronide showed a higher binding affinity to HSA than the (R)-glucuronide. The (S)-enantiomer of unmetabolized carprofen was bound to fatty acid free HSA to a much greater extent than the (R)-enantiomer. Warfarin reduced the binding of the glucuronides to a greater extent than did diazepam, but diazepam displaced the unconjugated enantiomers to a greater extent than did warfarin. These results suggest differences in binding region between the carprofen enantiomers and their glucuronides on the albumin molecule.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / metabolism*
  • Binding Sites
  • Carbazoles / metabolism*
  • Glucuronates / metabolism*
  • Humans
  • Serum Albumin / metabolism*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Ultrafiltration

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Carbazoles
  • Glucuronates
  • Serum Albumin
  • carprofen